Helbling B, von Overbeck J, Lauterburg B H
Department of Clinical Pharmacology, University of Bern, Switzerland.
Eur J Clin Invest. 1996 Jan;26(1):38-44. doi: 10.1046/j.1365-2362.1996.88237.x.
Low glutathione (GSH) in patients with HIV infection could contribute to their immune deficiency since GSH plays an important role in the function of lymphocytes and sulphydryls decrease the expression of HIV in vitro. In order to gain more insight into the mechanisms responsible for the deranged sulphydryl homeostasis in HIV infection, the release of GSH into the circulation, an estimate of the systemic production of GSH, was determined using a pharmacokinetic approach. The basal plasma concentrations of free GSH (3.3 +/- 1.3 vs. 5.3 +/- 1.9 mumol L(-1)) and cysteine (7.7 +/- 2.6 vs. 13.4 +/- 4.9 mumol L(-1)) were significantly lower in eight HIV-infected patients than in eight controls. Upon infusion of GSH at a constant rate of 1 mumol min-1 kg-1, GSH in plasma reached a new plateau. The increment in plasma GSH was significantly larger in the HIV-infected patients than in the controls. The input of GSH into the circulation (12.9 +/- 5.7 vs. 30.1 +/- 11.7 mumol min-1; P < 0.01) and the clearance of GSH (25 +/- 7 vs. 35 +/- 7 mL min-1 kg-1) were significantly lower in patients with HIV-infection. During infusion of GSH the concentration of cysteine in peripheral blood mononuclear cells of the HIV-infected patients increased significantly. Nevertheless, intracellular GSH did not increase. Thus, the consumption of GSH is not increased in HIV infection. Rather, the present data suggest that GSH in patients with HIV infection is low because of a decreased systemic synthesis of GSH.
HIV感染患者体内谷胱甘肽（GSH）水平较低，这可能导致其免疫缺陷，因为GSH在淋巴细胞功能中起重要作用，且巯基可在体外降低HIV的表达。为了更深入了解HIV感染中巯基稳态紊乱的机制，采用药代动力学方法测定了GSH释放到循环中的量，以此估算GSH的全身生成情况。8名HIV感染患者的游离GSH基础血浆浓度（3.3±1.3 vs. 5.3±1.9 μmol L⁻¹）和半胱氨酸浓度（7.7±2.6 vs. 13.4±4.9 μmol L⁻¹）显著低于8名对照组。以1 μmol min⁻¹ kg⁻¹的恒定速率输注GSH后，血浆GSH达到新的平台期。HIV感染患者血浆GSH的增量显著大于对照组。HIV感染患者GSH进入循环的量（12.9±5.7 vs. 30.1±11.7 μmol min⁻¹；P<0.01）和GSH清除率（25±7 vs. 35±7 mL min⁻¹ kg⁻¹）显著较低。在输注GSH期间，HIV感染患者外周血单核细胞中的半胱氨酸浓度显著增加。然而，细胞内GSH并未增加。因此，HIV感染时GSH的消耗并未增加。相反，目前的数据表明，HIV感染患者GSH水平较低是由于GSH的全身合成减少。
